The overall objective of this Program Project is the assessment of the role of monoclonal antibodies (MAbs) in the diagnosis, detection, and treatment of cancer. This program will focus on gastrointestinal cancers, most notably pancreatic and colorectal cancers. The Program addresses important issues in the use of antibodies on basic laboratory, preclinical, and clinical levels. Several investigators in this Program have nearly 20 years experience in the use of antibodies directed against gastrointestinal cancers. An antibody developed in this Project has a high degree of specificity for pancreatic cancer. This Project will continue its investigation of 2 antigens associated with pancreatic and colon cancers, and will refine and further test a serological immunoassay for pancreatic cancer. Preclinical studies will continue to probe for new ways to enhance the biological activity of radiolabeled antibodies. The clinical project will evaluate humanized antibodies labeled with 131I- and 90Y- as possible therapeutic agents. as well as examine several new constructs that may improve imaging. A new Project has been added to the Program. It will focus on the development of humanized antibodies, in addition to several new variants that may have diagnostic and therapeutic benefits. Humanized antibodies will reduce the immunogenicity that has been problematic for murine antibodies. In the previous year, a humanized antibody to carcinoembryonic antigen was developed and tested. A pilot clinical study determined that this agent is less immunogenic than the murine antibody. but retains excellent targeting properties. Thus, this is a highly integrated Program, supported by a number of important core laboratories. Collectively, this Program Project will help lead the way for developing new strategies for MAb-mediated detection and therapy of pancreatic and colorectal cancers.